2-DG Re-Normalized IFN-γ Production in T Cells Excluding TEMRA Cells from Patients with Aplastic Anemia

摘要

Aplastic anemia (AA) is a T cell immune mediated autoimmune disease in which cytokines, particularly IFN-? are pathogenesis factors. Glucose metabolism is closely related to effector functions of activated T cells, such as IFN-? production. The characteristics of glucose metabolism and whether interfering with glucose metabolism could affect T cells produce IFN-? ability in AA patients remains unknown. In this study, we examined the characteristics of glucose metabolism in T cells from AA patients and the effects of the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG) on the ability of T cell production IFN-?. Our data demonstrated abnormal glucose metabolism in stimulated T cells from AA patients, mainly reflected by increased glucose uptake and lactate secretion. In addition, EM and T-EMRA cells exhibit higher glucose uptake in patients with AA compared with healthy individuals. Moreover, the frequency of IFN-?(+) was reduced by 2-DG in T cell from AA patients. Unexpectedly, 2-DG re-normalized the frequency of IFN-?(+) in other T cell subsets, except for in the T-EMRA. In conclusion, our study reveals for the first time the existence of enhanced aerobic glycolysis in T cells from AA patients, and different T cell subsets exhibit different extent glucose uptake requirements. Aerobic glycolysis regulation may be a potential therapeutic strategy for aberrant T cell immunity. Moreover, T-EMRA may have specific metabolic abnormalities, which should receive more attention in future targeted immune metabolism research.

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